Multimodal neuroimaging investigation of brain ageing biomarkers in late life depression

Understanding the aetiology of medial temporal lobe (MTL) pathology in severe late-life depression (LLD) is crucial for improving diagnostic specificity with respect to dementia and for optimizing treatment. Given the role of tau in neurodegenerative diseases and our recent finding that hippocampal atrophy in LLD is not related to brain amyloid, we will study non-amyloid pathological brain aging in LLD using PET-MRI neuroimaging. We will investigate the relationship between white matter lesions, which are implicated in LLD, synaptic density in the hippocampus, and tau pathology and the association with stress. Importantly, we will also study how these findings impact upon treatment and behaviour, by investigating (a) if electroconvulsive therapy alters hippocampal synaptic density and whether this explains its therapeutic effect and its effect on hippocampal volume, and (b) if MTL atrophyin LLD is associated with failure of the emotional positivity effect that characterizes normal aging.